Translation-Associated Mutational U-Pressure in the First ORF of SARS-CoV-2 and Other Coronaviruses

• DOI: 10.3389/fmicb.2020.559165
• Publication Date: 2020-09-22T04:27:58Z
• Authors: Vladislav Victoro...; Rajanish Giri; Tatyana Aleksandr...; Shivani Krishna K...; Aleksander Nicola...; Victor Vitoldovic...
• Keywords: ORFS; Silent mutation; Cytosine; Translational frameshift; Synonymous substitution

Within 4 months of the ongoing COVID-19 pandemic caused by SARS-CoV-2, more than 250 nucleotide mutations have been detected in ORF1ab virus isolated from infected persons different parts globe. These observations open up an obvious question about rate and direction mutational pressure for further vaccine therapeutics designing. In this study, we did a comparative analysis ORF1a ORF1b using first isolate (Wuhan strain) as parent sequence. We observed that most are C to U transitions. The synonymous transitions is significantly higher non-synonymous ones, indicating negative selection on amino acid substitutions. Further, trends usage bias investigated 49 coronaviruses species. A strong fourfold degenerate sites toward uracil residues seen all studied coronaviruses: both translated thanks programmed ribosomal frameshifting has efficiency 14 - 45% substantial U-pressure perhaps because frequently ORF1b. Mutational there even ORFs not genomic RNA plus strands, but weaker ORF1ab. Unlike other mutations, cytosine deamination, mostly occurring during strand replication also translation, cannot be corrected proof-reading machinery coronaviruses. knowledge generated becomes stronger translation viral strands implications nucleoside analog development treating coronavirus infections.